PROJECT SUMMARY A crucial function of the central nervous system is to guide behavior toward events and outcomes that hold relevance for survival. This involves learning about stimuli in the environment that signal the availability of reward. Stimulus generalization allows us to apply stimulus-reward associations that we have acquired for one specific stimulus to similar stimuli encountered at a later time. Moreover, what we learn in one environment is not necessarily adaptive in a different environment, rendering such associations context-dependent. Importantly, generalization and context-dependent processing play a key role in the development and maintenance of drug addiction, as they represent fundamental aspects of reward-related behavior. With recent developments in pattern-based analysis of functional magnetic resonance imaging (fMRI) data, we are now in a position to explore the neural mechanisms of context-dependent stimulus generalization in humans. The objective of the current research proposal is to capitalize on these novel methods in order to understand the neural mechanisms of context-dependent associative learning and approach behavior. Specifically, we will use functional and structural brain imaging in combination with olfactory stimulation to reveal how a change in odor context from training to test modulates neural processing of stimuli that are perceptually similar (but not identical) to the original conditioned stimulus. The proposed experiments will test the effects of context on stimulus generalization gradients in the human striatum, reveal how context variables are represented in the brain, and identify the neural pathways by which context influences parameters of generalization. Together these experiments will open a new window into understanding context-dependent reward learning in the human brain. Critically, the findings of this research may lead to a better understanding of the neural systems that are altered in drug addiction, and should also inform future human addiction research and the development of novel diagnostic and therapeutic approaches.